Brigham K L, Meyrick B
Am Rev Respir Dis. 1986 May;133(5):913-27.
Two things are certain: endotoxin has dramatic effects on the structure and function of the lungs in intact animals and also on isolated lung cells, and both the in vivo and in vitro effects of endotoxin are complex. In whole animals, endotoxin causes obvious and subtle effects on functions of both airways and the pulmonary circulation. These effects include diffuse lung inflammation and injury of pulmonary vascular endothelium. Endotoxin can also directly injure endothelial cells in vitro. In vivo, lung injury caused by endotoxin is at least partly dependent on the presence of granulocytes, and some evidence also suggests that both lymphocytes and macrophages may participate in the response either directly or by directing cell traffic. At least in the sheep preparation, platelets do not seem to play a major role in the lungs' response to endotoxemia. Although endotoxin can activate complement and activated complement infused into whole animals affects the lungs, it seems unlikely that complement activation alone is sufficient to explain the severe and prolonged lung injury caused by endotoxin. Cyclooxygenase metabolites of arachidonic acid appear to mediate both changes in lung mechanics and pulmonary vasoconstriction after endotoxemia. Lipoxygenase products may play a role in these responses as well as the inflammatory response and increases in vascular permeability, although evidence for these latter speculations is not firm. Lung cell injury caused by endotoxin probably is mediated at least in part by generation of free radicals. Inflammatory cells, especially neutrophils, are one source of these toxic oxygen species, but intracellular generation of free radicals within lung cells per se may also be stimulated by endotoxin and account for some of the lung injury. Likewise, inflammatory-cell-derived proteinases may mediate endotoxin-induced injury of lung cells and, as with chronic lung diseases, balance between proteinases and antiproteinases could be important. The fact that free radicals can inactivate antiproteinases, and antiproteinases can act as free radical scavengers, may suggest a complex relationship among the several possible mediators of toxicity. Cyclic nucleotide metabolism is affected in whole animals and isolated lung cells by endotoxin and these classic second messengers could be involved in the pathogenetic sequence, but exactly how is unclear. Chronic effects of endotoxin on the lungs may provide a pathogenetic link between acute lung injury and chronic changes in lung structure and function.(ABSTRACT TRUNCATED AT 400 WORDS)
内毒素对完整动物的肺结构和功能以及对分离的肺细胞均有显著影响，而且内毒素的体内和体外效应都很复杂。在整体动物中，内毒素对气道和肺循环功能会产生明显和细微的影响。这些影响包括弥漫性肺炎症和肺血管内皮损伤。内毒素在体外也能直接损伤内皮细胞。在体内，内毒素引起的肺损伤至少部分取决于粒细胞的存在，而且一些证据还表明淋巴细胞和巨噬细胞可能直接或通过引导细胞运输参与这一反应。至少在绵羊实验中，血小板似乎在肺对内毒素血症的反应中不起主要作用。虽然内毒素能激活补体，且将激活的补体注入整体动物会影响肺，但仅补体激活似乎不足以解释内毒素所致的严重且持久的肺损伤。花生四烯酸的环氧化酶代谢产物似乎介导了内毒素血症后肺力学的变化和肺血管收缩。脂氧合酶产物可能在这些反应以及炎症反应和血管通透性增加中起作用，尽管后一种推测的证据并不确凿。内毒素所致的肺细胞损伤可能至少部分是由自由基的产生介导的。炎症细胞，尤其是中性粒细胞，是这些毒性氧物种的一个来源，但肺细胞内本身的自由基产生也可能被内毒素刺激，并导致部分肺损伤。同样，炎症细胞衍生的蛋白酶可能介导内毒素诱导的肺细胞损伤，并且与慢性肺部疾病一样，蛋白酶和抗蛋白酶之间的平衡可能很重要。自由基能使抗蛋白酶失活，而抗蛋白酶能作为自由基清除剂，这一事实可能表明几种可能的毒性介质之间存在复杂的关系。内毒素会影响整体动物和分离的肺细胞中的环核苷酸代谢，这些经典的第二信使可能参与发病过程，但具体机制尚不清楚。内毒素对肺的慢性影响可能在急性肺损伤与肺结构和功能的慢性变化之间提供一个发病学联系。（摘要截选至400字）
